CHOLESTEROL AND ITS IMPORTANCE

Cholesterol is an important lipid found in the cell membrane. It is a sterol, which means that cholesterol is a combination of a steroid and an alcohol .

It is an important component of cell membranes and is also the basis for the synthesis of other steroids, including the sex hormones estradiol and testosterone, as well as other steroids such as cortisone and vitamin D.

In the cell membrane, the steroid ring structure of cholesterol provides a rigid hydrophobic structure that helps boost the rigidity of the cell membrane.

Without cholesterol the cell membrane would be too fluid. In the human body, cholesterol is synthesized in the liver.

Cholesterol is insoluble in the blood, so when it is released into the blood stream it forms complexes with lipoproteins.

Cholesterol can bind to two types of lipoprotein, called high-density lipoprotein (HDL) and low-density lipoprotein (LDL).

A lipoprotein is a spherical molecule with water soluble proteins on the exterior. Therefore, when cholesterol is bound to a lipoprotein, it becomes blood soluble and can be transported throughout the body.

HDL cholesterol is transported back to the liver. If HDL levels are low, then the blood level of cholesterol will increase.

High levels of blood cholesterol are associated with plaque formation in the arteries, which can lead to heart disease and stroke.

Proteins are complex macromolecules composed of amino acids that perform diverse biological functions. Understanding their structure-function relationships is crucial for medical applications and biochemistry.

Levels of Protein Structure

Primary Structure

• Linear sequence of amino acids connected by peptide bonds
• Determines all higher levels of organization
• Coded by DNA sequence

Secondary Structure

• Local folding patterns stabilized by hydrogen bonds
• Alpha helix: Right-handed spiral structure
• Beta sheet: Extended polypeptide chains arranged side by side
• Beta turn: Connects different secondary structural elements

Tertiary Structure

• Three-dimensional folding of entire polypeptide chain
• Stabilized by:
  • Hydrogen bonds
  • Disulfide bridges
  • Van der Waals forces
  • Electrostatic interactions
  • Hydrophobic interactions

Quaternary Structure

• Assembly of multiple polypeptide subunits
• Present only in proteins with more than one polypeptide chain
• Examples: Hemoglobin (4 subunits), antibodies

Protein Classification

Based on Structure

1. Fibrous Proteins

   • Elongated, insoluble
   • Structural functions
   • Examples: Collagen, keratin, elastin

2. Globular Proteins

   • Compact, soluble
   • Functional proteins
   • Examples: Enzymes, antibodies, hormones

Based on Composition

1. Simple Proteins

   • Composed only of amino acids
   • Examples: Albumin, globulins

2. Conjugated Proteins

   • Contain non-protein prosthetic groups
   • Glycoproteins: Contain carbohydrates
   • Lipoproteins: Contain lipids
   • Nucleoproteins: Contain nucleic acids
   • Phosphoproteins: Contain phosphate groups
   • Metalloproteins: Contain metal ions

Factors regulating blood calcium level

(i) Vitamin D

(a) Vitamin D and absorption of calcium: Active form of calcium is calcitriol. Calcitriol enters intestinal wall and binds to cytoplasmic receptor and then binds with DNA causes depression and consequent transcription of gene code for calbindin. Due to increased availability of calbindin, absorption of calcium increases leading to increased blood calcium level.
(b) Vitamin D and Bone: Vitamin D activates osteoblast, bone forming cells & also stimulates secretion of alkaline phosphatase. Due to this enzyme, calcium and phosphorus increase.

(c) Vitamin D and Kidney: Calcitriol increase reabsorption of calcium and phosphorus by renal tubules.

(ii) Parathyroid  hormone (PTH)

Normal PTH level in serum is 10-60ng/l.

(a) PTH and bones: In bone, PTH causes demineralization. It also causes recreation of collagenase from osteoclast  leads to loss of matrix and bone resorption. As a result, mucopolysacharides and hydroxyproline are excreted in urine.

(b) PTH and Kidney: In kidney, PTH causes increased reabsorption of calcium but decreases reabsorption of phosphorus from kidney tubules.

(iii) Calcitonin Calcitonin decreases serum calcium level. It inhibits resorption of bone. It decreases the activity of osteoclasts and increases osteoblasts.

Hyper Calcemia When plasma Ca2+ level is more than 11mg/dl is called Hypercalcemia. It is due to parathyroid adenoma or ectopic PTH secreting tumor. calcium excreted in urine decreases excretion of chloride causing hyperchloremic acidosis.

Hypocalcemia Plasma calcium level less than 8mg/dl is called hypocalcemia. Tetany due to accidental surgical removal of parathyroid glands or by autoimmune disease. In tetany, neuromuscular irritability is increased. Increased Q-7 internal in ECG is seen. Main manifestation is carpopedal spasm. Laryngismus and stridor are also observed.

Clinical significance

Primary hyperparathyroidism is due to autonomous, abnormal hypersecretion of PTH in the parathyroid gland

Secondary hyperparathyroidism is an appropriately high PTH level seen as a physiological response to hypocalcemia.

A low level of PTH in the blood is known as hypoparathyroidism and is most commonly due to damage to or removal of parathyroid glands during thyroid surgery.

Amino Acid Catabolism

Glutamine/Glutamate and Asparagine/Aspartate Catabolism

Glutaminase is an important kidney tubule enzyme involved in converting glutamine (from liver and from other tissue) to glutamate and NH₃⁺, with the NH₃⁺ being excreted in the urine. Glutaminase activity is present in many other tissues as well, although its activity is not nearly as prominent as in the kidney. The glutamate produced from glutamine is converted to a-ketoglutarate, making glutamine a glucogenic amino acid.

Asparaginase is also widely distributed within the body, where it converts asparagine into ammonia and aspartate. Aspartate transaminates to oxaloacetate, which follows the gluconeogenic pathway to glucose.

Glutamate and aspartate are important in collecting and eliminating amino nitrogen via glutamine synthetase and the urea cycle, respectively. The catabolic path of the carbon skeletons involves simple 1-step aminotransferase reactions that directly produce net quantities of a TCA cycle intermediate. The glutamate dehydrogenase reaction operating in the direction of a-ketoglutarate production provides a second avenue leading from glutamate to gluconeogenesis.

Alanine Catabolism

Alanine is also important in intertissue nitrogen transport as part of the glucose-alanine cycle. Alanine's catabolic pathway involves a simple aminotransferase reaction that directly produces pyruvate. Generally pyruvate produced by this pathway will result in the formation of oxaloacetate, although when the energy charge of a cell is low the pyruvate will be oxidized to CO₂ and H₂O via the PDH complex and the TCA cycle. This makes alanine a glucogenic amino acid.

Arginine, Ornithine and Proline Catabolism

The catabolism of arginine begins within the context of the urea cycle. It is hydrolyzed to urea and ornithine by arginase.

Ornithine, in excess of urea cycle needs, is transaminated to form glutamate semialdehyde. Glutamate semialdehyde can serve as the precursor for proline biosynthesis as described above or it can be converted to glutamate.

Proline catabolism is a reversal of its synthesis process.

The glutamate semialdehyde generated from ornithine and proline catabolism is oxidized to glutamate by an ATP-independent glutamate semialdehyde dehydrogenase. The glutamate can then be converted to α-ketoglutarate in a transamination reaction. Thus arginine, ornithine and proline, are glucogenic.
 

Methionine Catabolism

The principal fates of the essential amino acid methionine are incorporation into polypeptide chains, and use in the production of α -ketobutyrate and cysteine via SAM as described above. The transulfuration reactions that produce cysteine from homocysteine and serine also produce α -ketobutyrate, the latter being converted to succinyl-CoA.

Regulation of the methionine metabolic pathway is based on the availability of methionine and cysteine

Phenylalanine and Tyrosine Catabolism

Phenylalanine normally has only two fates: incorporation into polypeptide chains, and production of tyrosine via the tetrahydrobiopterin-requiring phenylalanine hydroxylase. Thus, phenylalanine catabolism always follows the pathway of tyrosine catabolism. The main pathway for tyrosine degradation involves conversion to fumarate and acetoacetate, allowing phenylalanine and tyrosine to be classified as both glucogenic and ketogenic.

Tyrosine is equally important for protein biosynthesis as well as an intermediate in the biosynthesis of several physiologically important metabolites e.g. dopamine, norepinephrine and epinephrine

Classification of Fatty Acids and Triglycerides

Short-chain: 2-4 carbon atoms

Medium-chain: 6-12 carbon atoms

Long-chain: 14-20 carbon atoms

Very long-chain: >20 carbon atoms

• are usually in esterified form as major components of other lipids

A16-carbon fatty acid, with one cis double bond between carbon atoms 9 and 10 may be represented as 16:1 cisD⁹.

Double bonds in fatty acids usually have the cis configuration. Most naturally occurring fatty acids have an even number of carbon atoms

Examples of fatty acids

There is free rotation about C-C bonds in the fatty acid hydrocarbon, except where there is a double bond. Each cis double bond causes a kink in the chain,